Artful Taste Masking Improves Patient Compliance

Artful Taste Masking Improves Patient Compliance

By: Sundeep Sethia, Ph.D., Senior Director, R&D

Artful Taste Masking Improves

The flavor taste masking market is expected to jump from $224 million in 2021 to $331 million by 2028.1 One driver behind this increase comes from the pharma industry. According to a recent webinar, Solving the Taste-masking Challenge, more than 90 percent of pediatricians report that a drug’s taste and palatability are the biggest barriers to completing treatment and 11 percent of adverse events relate to abnormal taste or poor aftertaste.

Taste Masking is required for dosage form that interact with the taste buds, such as solutions, suspensions, powders, films, chewable tablets, and orally disintegrating tablets – the preferred dosage forms for pediatric and geriatric populations. Traditional coated tablets, capsules, and softgels interact minimally with the taste buds as they are swallowed, hence most drugs in these dosage forms do not require taste masking. The best and most practical method of taste masking should be considered for each API. Some of these methods are discussed below.

Taste Masking 6

Sweeteners & Flavoring Agents

Flavors and sweeteners (natural or synthetic) are the most common and easiest ways to mask taste, especially in liquid formulas and chewable tablets. Natural sweeteners include sucrose, glucose, fructose, sorbitol, mannitol, glycerol, honey, and liquor ice. Artificial sweeteners include saccharin, saccharin sodium, aspartame, and sucralose. Sweeteners promote a cooling sensation on the esophageal surface, Note: This method is not very effective for very bitter and water-soluble drugs.

Taste Masking 8

Lipids

Lipids have found extensive use as functional excipients in taste masking because:

  • They control drug release in the oral cavity, preventing buildup of a concentration higher than the bitterness threshold;
  • They have a biocompatible nature, which increases their acceptability in the human body
  • They can alter pharmacokinetics of APIs by modulating release profiles; and
  • They have low melting points, ideal for incorporating drugs in methods like hot-melt extrusion, melt granulation, spray drying, and emulsification.

Selecting a lipid depends on its physiochemical properties and the desired quality of the dosage form. Lipid membrane taste sensors have been widely used in assessing taste and palatability of pharmaceutical formulations using electronic tongue (e-tongue).2

Taste Masking 4

Complexation and Inclusion Complexation

Complexation is especially applicable for liquid products (e.g. cyclodextrins, ion exchange resins). The purpose of the complexing agent is to mask the unpleasant taste of specific drug either by reducing its oral solubility or reducing the amount of the drug particles interacting with taste buds. One of the most popular approaches in the masking of the taste of bitter drugs is based on ion exchange resin complexes (IER). IER are the polyelectrolytes of the high molecular weight of solids, and, in a suitable insoluble form, can exchange their ions in movement the load equal to the surrounding medium.3 According to webinar, IER enables more flexible formulation of a bitter API. Generally, a weak cation or anion exchange resin is used for taste masking purposes so that the loosely bound drug is released in the gastrointestinal tract.

With complexation, IERs binds or exchange ions with the polymer, but does not necessarily engulf the molecule. With inclusion complexation, on the other hand, there is hydrophobic interaction between the API and the donut shaped cyclodextrin, which acts as the host and engulfs the API to prevent its exposure to the bulk solution. The complexing agent masks the bitter taste of the drug by either decreasing its oral solubility upon ingestion or decreasing the amount of drug particles exposed to taste buds, thereby reducing the perception of bitter taste. This method is most suitable for low dose drugs.4

Taste Masking 5

Coatings & Granulation

A coating or granulation prevents interaction of the harsh tasting medicine by blocking the drug contact with the taste buds in mouth. These taste maskers offer a physical wall around the medicine, and can be applied using:

  • Spray drying: Spray drying converts a feed from a fluid state – emulsion, suspension or solution – into dried particulate form by subjecting the feed to a hot drying medium. Dried particles are separated and collected in the form of microspheres in which the bitter drug is encapsulated/entrapped in a polymeric matrix. The spray-dried microspheres does not allow the drug to be released at salivary pH thus masking the bitterness in oral cavity. However, active drug is then rapidly released afterwards in gastric fluids. Thus, the taste is masked without interferingwith the release of drug in gastric environment, which makes spray drying a suitable technique for taste masking immediate-release oral dosage forms.5
  • Fluid Bed Granulation: A fluidized bed processor (agglomeration) is among highly efficient and simple methods of masking drug taste in formulations pediatric, tablets chewable, and liquid formulations liquid. The method involves fluidizing fine powders up to 50μm in expansion chambers through fast-moving hot air.6 Drug particles gush from the top of the expansion chamber with a spray nozzle and get covered with the coating solution on their way to the bottom. The coated granules are then dried in hot air.
  • High Shear Granulation: This method turns powders into dense granules and thereby reduces the effective surface area. Granulation with polymer solution that prevent quick release in the saliva can reduce the exposure of the API and improve the taste perception of the oral granules or tablet formulation. Alternatively, for extremely bitter drugs, the dried granules can be coated in fluid bed with various polymers of choice to mask the taste and tailor the release profile of the formulation.
  • Hot-melt Granulation: Pharmaceutical powders are efficiently agglomerated by the use of a low melting point binder, generally wax or lipid-based, which is added to the other components of the powder. At molten state, the binder acts as a granulating liquid and coats the drug to mask the taste.
Taste Masking 7

Emulsions

Masking the bitter taste of the drug using multiple emulsions technique is also a good approach. This technique is achieved by dissolving the active pharmaceutical ingredient in the inner aqueous phase of w/o/w emulsion. The internal aqueous phase and the external aqueous phase are separated by the oil phase. Another type is o/w/o emulsion, in which water globules contain oil globules. The effectiveness of masking the bitter taste using both types of multiple emulsions is high.8

Taste Masking 3

Tips for Choosing a Taste Masking Method

No matter the taste masking method chosen, a skilled contract development and manufacturing organization (CDMO) will take the following into account as they formulate the ideal taste masker for an API3:

  • Minimal equipment and processing steps;
  • Dosage delivery options (solution vs. suspension vs. granules/tablet)
  • No effect to the bioavailability of the drug;
  • Fewer excipients are needed to get the best formulation;
  • Affordable raw materials;
  • Reduced production costs; and
  • Quick and easy preparation.

Most importantly, keep in mind that the appropriate choice of masking substance completely hides, anesthetizes, or changes the flavor of the sour tasting drug without altering the delivery mechanism of the drug. It is important to partner with an experienced CDMO that has the masking methods, uses state-of-the-art technology, and understands the art and science of taste masking.

References

Talk to a Pii Scientist

ABOUT Pii

Pharmaceutics International, Inc. (Pii) is a US-based contract development and manufacturing organization (CDMO) located in Hunt Valley, Maryland. The experienced scientists, engineers, and staff at Pii pride themselves on adroitly employing a phase appropriate method of drug development for the prudent use of their client’s resources as they solve challenging problems. In addition to offering end-to-end development services, Pii manufactures a variety of dosage forms to include complex parenteral drugs and has a wealth of analytical testing capabilities. Its Hunt Valley campus has four aseptic suites with lyophilization capabilities. Our talented professionals stand ready to help!

Sundeep Sethia

Sundeep Sethia, Ph.D.
Senior Director, R&D

Sundeep Sethia joined Pii in September 2018 as Senior Director of Pharmaceutical R&D. He has over 15 years of experience in the pharmaceutical industry.

Dr. Sethia formerly served as the Director of Pharmaceutical R&D at Amneal Pharmaceuticals. Prior to Amneal, he held positions of increasing responsibility at both Teva and Barr Laboratories in R&D. His expertise is in drug development across a broad range of therapeutic areas and dosage forms. He has a proven track record in generic drug development and approvals.

Dr. Sethia received his Ph.D. in Pharmaceutical Sciences from St. John’s University, NY. He earned a Master’s and a Bachelor’s degree in Biotechnology and Pharmacy, respectively from Jadavpur University in India. He has co-authored various peer-reviewed scientific publications and patents/patent applications.